Brl 44408

Animals were randomly allocated into seven groups (n = 8 each) as follows. (1)

Sham group (group S) rats subjected to abdomen dissection and isolation of the hepatic peripheral vessels without occlusion;

(2)

Model group (group M) rats underwent the OALT procedure as described above, and no drug was utilized;

(3)

Low-dose Dex group (group D1) and high-dose Dex group (group D2) rats received 10 or 50 μg/kg Dex (Hengrui Pharmaceutical Co., Ltd., Nanjing, China), respectively, via intraperitoneal injection 30 min before the operation; and

(4)

Atipamezole + high-dose Dex group (group B1), ARC-239 + high-dose Dex group (group B2), and BRL-44408 + high-dose Dex group (group B3) rats received 500 μg/kg Atipamezole (a nonspecific α₂ receptor blocker, Sigma-Aldrich, St. Louis., MO, USA), 50 μg/kg ARC239 (a specific α_2B/C receptor blocker, Santa Cruz Biotechnology, Santa Cruz, CA, USA), or 1.5 mg/kg BRL-44408 (a specific α_2A receptor blocker, Sigma-Aldrich), respectively, via intraperitoneal injection 10 min before receiving 50 μg/kg Dex 30 min prior to the OALT.

In the current study, all the drugs were dissolved in normal saline. Based on previous studies, Dex was administered 30 min before or immediately after the liver IR injury [16 (link),19 (link)]. The dose selected for each antagonist was on the basis of the antagonist’s affinity and the dose-effect relationship with Dex.

Male Sprague-Dawley rats (8–10 weeks old and 220–250 g) were purchased from the Medical Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. Fifty-six rats were randomized into seven groups (n = 8 per group). Rats in the sham-operated group (S) did not undergo OALT. Rats in the model group (M) were intraperitoneally injected with saline 30 min before OALT. Rats in the D1 and D2 groups were intraperitoneally injected with 10 μg/kg (drug/body weight) and 50 μg/kg Dex (Hengrui Pharmaceutical Co., Ltd., Jiangsu, China) 30 min before OALT, respectively. Rats in the B1, B2, and B3 groups were intraperitoneally injected with 500 g/kg atipamezole (a nonspecific α_2A-AR siRNA blocker, Sigma-Aldrich, USA), 50 g/kg ARC239 (a specific α_2B/C-AR blocker, Santa Cruz Biotechnology, Inc., USA), and 1.5 mg/kg BRL-44408 (a specific α_2A-AR siRNA blocker, Sigma-Aldrich, USA) 40 min before receiving 50 μg/kg Dex prior to OALT, respectively. This study was performed with the approval of the Institutional Animal Care and Use Committee of Sun Yat-sen University in Guangzhou, China, and in accordance with the principles stated in the Guide for the Care and Use of Laboratory Animals.